Lemons add zest to drug delivery

Spiking certain drugs with vitamin C could improve treatments for epilepsy, Alzheimer's, Parkinson's and other disorders, say Italian researchers. The vitamin, ascorbic acid, fast tracks several drugs past the brain's molecular customs desk, while drugs that are normally barred can be smuggled through.

The brain has a strict control system for the passage of molecular traffic, known as the blood-brain barrier. This barrier is composed of membranes and channels that help filter out potentially harmful compounds in the blood before they can damage the brain. But, it also allows nutrients, such as vitamins and minerals, free entry. Without the blood-brain barrier, our brains would be poisoned by the plethora of toxic waste products circulating in the blood.

Now, Stefano Manfredini of the University of Ferrara in Italy, believes he and his team have "opened a door for a promising new way to improve delivery of drugs into the brain." Their technique relies on the natural nutrient - ascorbic acid -in fruit and vegetables and normally associated with preventing scurvy.

Other researchers recently discovered that some cells carry a protein receptor, known as the SVCT2 transporter. These receptors are present in the blood-brain barrier. They carry this essential antioxidant vitamin directly into the brain, where it is needed in large amounts. One of the vitamin's natural functions is to assist in mopping up dangerous free radicals that form as by-products of normal brain activity. Manfredini's team reasoned that if vitamin C could enter the brain easily, maybe it could smuggle in other chemicals.

The team studied three compounds: "Diclofenamic acid, nipecotic acid and kynurenic acid are all well known as having difficulty crossing the blood-brain barrier," explains Manfredini. "In particular, the latter two compounds could be useful to treat brain disorders but are not able to reach the target organ." The team used cells extracted from the human eye known as retinal pigment epithelial cells, which are rich in the vitamin C transporter units.

Manfredini believes this laboratory model - developed in collaboration with Puttur Prasad at the Medical College of Georgia - would mimic the barrier and allow them to predict how well any of the drugs would be smuggled into the brain. Nipecotic and kynurenic acids do not naturally interact with the transporter, and diclophenamic acid normally blocks vitamin C transport, but with their vitamin C smuggler attached, all three drugs interact readily with the transporter without blocking vitamin C.

Preliminary experiments with nipecotic acid on mice with epilepsy had no effect on their convulsions, as expected, but when the drug attached to vitamin C was injected, the convulsions were delayed, with few side effects. Tests on people are yet to be done but the researchers are excited that they may have found a way to open up the brain's border control. Manfredini believes the approach could be used to carry drugs as diverse as antiviral agents (including those for treating Aids) and for treating neurodegenerative diseases such as Alzheimer's, Parkinson's and epilepsy. The team is now investigating how vitamin C is such a good drug smuggler.

· David Bradley is a writer at sciencebase.com

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